Department of Endocrinology, St. Vincent's University Hospital, Dublin, Ireland.
PLoS One. 2010 Jan 25;5(1):e8660. doi: 10.1371/journal.pone.0008660.
Obese individuals who smoke have a 14 year reduction in life expectancy. Both obesity and smoking are independently associated with increased risk of malignancy. Natural killer cells (NK) are critical mediators of anti-tumour immunity and are compromised in obese patients and smokers. We examined whether NK cell function was differentially affected by cigarette smoke in obese and lean subjects.
Clinical data and blood were collected from 40 severely obese subjects (BMI>40 kg/m(2)) and 20 lean healthy subjects. NK cell levels and function were assessed using flow cytometry and cytotoxicity assays. The effect of cigarette smoke on NK cell ability to kill K562 tumour cells was assessed in the presence or absence of the adipokines leptin and adiponectin. NK cell levels were significantly decreased in obese subjects compared to lean controls (7.6 vs 16.6%, p = 0.0008). NK function was also significantly compromised in obese patients (30% +/- 13% vs 42% +/-12%, p = 0.04). Cigarette smoke inhibited NK cell ability to kill tumour cell lines (p<0.0001). NK cells from obese subjects were even more susceptible to the inhibitory effects of smoke compared to lean subjects (33% vs 28%, p = 0.01). Cigarette smoke prevented NK cell activation, as well as perforin and interferon-gamma secretion upon tumour challenge. Adiponectin but not leptin partially reversed the effects of smoke on NK cell function in both obese (p = 0.002) and lean controls (p = 0.01).
CONCLUSIONS/SIGNIFICANCE: Obese subjects have impaired NK cell activity that is more susceptible to the detrimental effects of cigarette smoke compared to lean subjects. This may play a role in the increase of cancer and infection seen in this population. Adiponectin is capable of restoring NK cell activity and may have therapeutic potential for immunity in obese subjects and smokers.
肥胖且吸烟的个体预期寿命会减少 14 年。肥胖和吸烟均与恶性肿瘤风险增加独立相关。自然杀伤细胞（NK）是抗肿瘤免疫的重要介质，在肥胖患者和吸烟者中受到损害。我们研究了在肥胖和非肥胖个体中，香烟烟雾是否会对 NK 细胞功能产生不同的影响。
从 40 名严重肥胖个体（BMI>40 kg/m²）和 20 名健康非肥胖个体中采集临床数据和血液。使用流式细胞术和细胞毒性测定法评估 NK 细胞水平和功能。在存在或不存在脂肪因子瘦素和脂联素的情况下，评估香烟烟雾对 NK 细胞杀伤 K562 肿瘤细胞能力的影响。与非肥胖对照者相比，肥胖个体的 NK 细胞水平显著降低（7.6%比 16.6%，p=0.0008）。肥胖患者的 NK 功能也明显受损（30%±13%比 42%±12%，p=0.04）。香烟烟雾抑制 NK 细胞杀伤肿瘤细胞系的能力（p<0.0001）。与非肥胖者相比，肥胖者的 NK 细胞对烟雾的抑制作用更敏感（33%比 28%，p=0.01）。香烟烟雾阻止 NK 细胞在受到肿瘤刺激时的激活以及穿孔素和干扰素-γ的分泌。脂联素而非瘦素部分逆转了烟雾对肥胖者（p=0.002）和非肥胖者（p=0.01）NK 细胞功能的影响。
结论/意义：与非肥胖者相比，肥胖个体的 NK 细胞活性受损，且更易受到香烟烟雾的有害影响。这可能在该人群中增加癌症和感染的发生中发挥作用。脂联素能够恢复 NK 细胞的活性，并且可能对肥胖者和吸烟者的免疫具有治疗潜力。
